1. Field of the Invention:
The present invention relates to a long-acting local anesthetic and more particularly to an anesthetic formed by covalently linking a small molecule having local anesthetic activity to polyphosphazene.
2. Description of the Prior Art:
Many useful anesthetics and analgesics, such as codeine and procaine, have been developed for the treatment of persistent localized pain. However, such medicaments are not without their own problems. Systemic anesthetics affect the entire nervous system and are not useful for control of localized pain. Mild analgesics, such as aspirin, may be ineffective against severe pain while stronger analgesics, such as codeine and the related narcotics, produce many undesirable side effects.
One useful class of anesthetics for the treatment of localized pain is the local anesthetics. These are drugs that produce loss of sensation and motor activity in a restricted area of the body by reversibly blocking conduction in nerve fibers. However, such drugs often have undesirable side effects caused by their high concentration in the blood either at the point of injection or systemically. Such high concentration are needed initially since the known local anesthetics are short-lived and are metabolized in plasma or the liver. Even if only a low dose is needed to produce the desired degree of anesthetic, a higher dose must be administered in order to produce an anesthetic effect of suitable duration, since multiple injections traumatize the patient and are undesirable. Accordingly, there exists a need for a local anesthetic in a long-acting, slow-release form.
Various publications have disclosed long-acting medicaments of various types. For example, U.S. Pat. Nos. 3,887,699 to Yolles, 3,983,209 to Schmitt, and 4,130,639 to Shalaby et al have disclosed incorporation of a drug into a biodegradable polyester composition. Water-soluble or biodegradable polyorganophosphazenes have recently come into use in this area. The use of water-soluble polyorganophosphazenes as carriers for coordinatively bonded platinum-containing anti-cancer drugs is disclosed in Allen et al, J. Am. Chem. Soc., 99, 3987 (1977) and Allcock et al, ibid, 3984 (1977). Likewise, U.S. Pat. No. 4,239,755 to Allcock et al discloses a medicament comprising steroidal cyclotriphosphazenes.
The chemistry of polyphosphazene polymers, although not established to the extent known for organic polymers, is becoming better known. A recent review in this area indicative of the known chemistry of these macromolecules is Allcock, "High Polymeric Organophosphazenes," Contemporary Topics in Polymer Science, 3, 55 (1979) which is herein incorporated by reference.
However, none of these references disclose or suggest the preparation of a long-acting local anesthetic, and the need for such substances still exists.